Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microcystic adnexal carcinoma (MAC) is the prototype for a subset of locally aggressive adnexal carcinomas (LAACs). Ultraviolet radiation (UVR) and UVB signature p53 mutations are implicated in the etiology of the most common cutaneous carcinomas. However in MACs, the role of UVR and p53 mutations is unknown. In addition, controversy still exists regarding the patterns of differentiation within these tumors. The objective of this study was to determine the expression patterns of immunohistochemical markers for p53, Ki-67, c-erbB-2, and Bcl-2 in MACs, and to compare these patterns with two MAC histologic stimulants: sclerosing type basal cell carcinomas (sBCCs) and desmoplastic trichoepitheliomas (dTEs). Other objectives were to compare expression patterns of cytokeratin (CK) AE1/AE3, CK7, CD20, endothelial membrane antigen (EMA), Ber-EP4, CD34, alpha-smooth muscle actin (SMA), and S-100 protein in MACs with its histologic simulators, and to determine the usefulness of all the immunohistochemical studies in diagnosis. Immunohistochemical markers were performed on 10 MACs, 10 sBCCs, and four dTEs. They included p53, Ki-67, c-erbB-2, Bcl-2, CK AE1/AE3, CK7, CD20, EMA, Ber-EP4, CD34, S-100 protein, and alpha-SMA. MACs expressed p53 in less than 25% of the tumor cells in only two cases (20%), and both cases showed only moderately intense staining, whereas 80% of the sBCCs were positive and showed intense staining, and all dTEs were negative. In MACs, less than 5% of the tumor cells were Ki-67 positive, whereas the sBCCs showed 20% to 40% Ki-67-positive tumor cells and dTEs showed rare Ki-67-positive cells. Bcl-2 was expressed focally in MACs, diffusely in sBCCs, and in scattered cells in dTEs. All tumors were negative for c-erbB-2. CD34, CK7, EMA, Ber-EP4, S-100 protein, and alpha-SMA all showed a distinctive pattern of staining in MACs. Although MACs arise commonly in chronically sun-exposed skin, increased expression of p53 is not found frequently. Overexpression of c-erbB-2 does not appear to be a factor in the development and progression of these adnexal tumors. Bcl-2 is expressed in MACs, but not diffusely as in sBCCs. The low level of Ki-67 supports a low proliferative rate, and other immunohistochemical markers support divergent patterns of adnexal differentiation in MACs. Immunohistochemical studies may help to differentiate MAC from sBCCs and dTEs.
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PMID:Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis. 1125 20

Primary follicular lymphoma of the testis in childhood is extremely rare. To our knowledge, only 5 cases have been reported to date. We report a case in a 6-year-old boy who presented with painless right scrotal enlargement. Right radical orchiectomy revealed a follicular large cell lymphoma with diffuse areas confined to the testis and epididymis, clinical stage IE. Immunohistochemical stains demonstrated that the neoplastic cells were of B-cell lineage, positive for CD10, CD20, CD79a, and BCL-6. Staining for CD21 accentuated networks of dendritic reticulum cells within the nodules. The cells were negative for BCL-2, p53, and T-cell antigens. There was no evidence of the t(14;18) detected by polymerase chain reaction. The data suggest that follicular lymphoma of the testis in children has a different pathogenesis than follicular lymphoma in adults.
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PMID:Primary follicular large cell lymphoma of the testis in a child. 1126 Jun 36

Treatment of patients with non-Hodgkin's lymphoma (NHL) is frequently hampered by development of chemoresistance. Rituximab is a chimeric mouse antihuman CD20 antibody that offers an alternative; however, its mechanism of action is not clearly understood. Treatment of lymphoma cell lines with Rituximab sensitizes the cells to the cytotoxic and apoptotic effects of therapeutic drugs, e.g., cisplatin, fludarabine, vinblastine, and Adriamycin. This study investigated the mechanism(s) involved in the reversal of drug resistance by Rituximab therapy. NHL cells synthesize and secrete antiapoptotic cytokines implicated in drug resistance, including interleukin (IL)-6, IL-10, and tumor necrosis factor alpha. We hypothesized, therefore, that sensitization by Rituximab may be due in part to modification of cytokine production. In this study, examination of cytokine secretion by NHL 2F7 tumor cells revealed down-regulation of IL-10 by Rituximab treatment. Moreover, cytotoxicity assays using exogenous IL-10 and IL-10-neutralizing antibodies demonstrated that IL-10 serves as an antiapoptotic/protective factor in these tumor cells against cytotoxic drugs. Furthermore, expression in 2F7 cells of the protective factor, Bcl-2, was shown to be dependent on IL-10 levels and down-regulated by Rituximab. Other gene products such as Bax, Bcl-x, Bad, p53, c-myc, and latent membrane protein-1 (LMP) were not affected by Rituximab treatment. Drug sensitization, as well as down-regulation of both IL-10 and Bcl-2, was corroborated in experiments using the NHL cell line 10C9. The Ramos and Daudi NHL cell lines were not sensitizable, nor did their Bcl-2 or IL-10 levels change. These studies demonstrate that one mechanism by which Rituximab sensitizes NHL to chemotherapeutic drugs is mediated through down-regulation of antiapoptotic IL-10 autocrine/paracrine loops and Bcl-2. The clinical relevance of these findings is discussed.
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PMID:Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. 1129 68

Achalasia is an esophageal motor disorder in which the primary morphologic changes are found in the myenteric plexus. However, a number of secondary alterations are characteristically found in esophagectomy specimens, including the mucosa. In addition, these patients are at increased risk of developing esophageal squamous cell carcinoma. We studied the squamous mucosal alterations in 35 esophagectomy specimens from patients with end-stage achalasia and compared them with those found in the squamous mucosa near the esophagogastric junction from pediatric autopsies (</=18 years) from patients with no known esophageal disease. A representative block was immunostained for p53 (DO7), CD3, and CD20. p53 immunoreactivity was graded as follows: 0 = no staining; 1+ = rare basal cell staining; 2+ = extensive basal cell staining; 3+ = suprabasilar staining. Intraepithelial lymphocyte counts were performed by counting five high power fields (HPF) and calculating an average/HPF. Ages of achalasia patients at esophagectomy ranged from 21 to 78 years (mean 56 years), including 20 men and 15 women. Disease duration ranged from 1 to 44 years (mean 17 years). In all cases the squamous mucosa from achalasia patients was markedly hyperplastic with papillomatosis and basal cell hyperplasia. p53 staining in the squamous mucosa from achalasia patients was significantly more common than in controls (32 of 35 [91%] vs 1 of 17 [6%]; p <0.05). In all achalasia cases CD3+ cells far outnumbered CD20+ cells. There was a significantly greater number of CD3+ cells in achalasia cases (range 32-239/HPF; mean 107/HPF) compared with controls (range 0.8-12/HPF; mean 6/HPF) (p <0.05). In conclusion, the squamous mucosa in esophagectomy specimens from patients with end-stage achalasia shows significant alterations including marked squamous hyperplasia, an increased frequency of p53 immunoreactivity, and increased numbers of CD3+ cells when compared with controls. These changes may be related to the increased risk of squamous cell carcinoma in these patients.
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PMID:Squamous mucosal alterations in esophagectomy specimens from patients with end-stage achalasia. 1168 58

The HIV epidemic in the Asian subcontinent has a significant impact on India. Patients with AIDS have an increased risk of developing non-Hodgkin lymphoma (NHL). In this study, we have investigated the pattern of distribution of lymphoid neoplasms and also studied the Epstein-Barr virus (EBV)-association and p53 expression in 35 HIV-positive patients from India. The biopsy samples were studied for histology and for expression of CD20, CD3, CD15, CD30, light chains, CD138, bcl-6, epithelial membrane antigen, EBV-latent membrane protein-1, and p53 protein. In situ hybridization was performed with digoxigenin-labeled anti-sense EBV-encoded nuclear RNA-1 (EBER-1) probe. Polymerase chain reaction (PCR) was performed on DNA extracted from paraffin sections for EBV-subtype analysis. The 35 cases included 7 cases of Hodgkin disease (HD), 4 cases of plasmacytoma (PL), and 24 cases of NHL. Among the cases of NHL, 3 were Burkitt lymphoma (BL), 4 were diffuse large B-cell lymphoma (DLBL) of centroblastic type (CBL), 10 were DLBL of immunoblastic type (IBL), 4 were high-grade B-cell lymphoma (unspecified) and the rest were other subtypes. EBV-association was noted in all cases of HD, 2 of 3 BL, and 3 of 10 IBL. PCR analysis of the EBNA-3C gene revealed amplimers corresponding to type A. A p53 protein overexpression was noted in 6 of 10 IBLs, 1 of 3 BLs, 2 of 3 CBLs, and 5 of 7 cases of HD. This is the first reported study of lymphoid malignancies in HIV-positive individuals from India.
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PMID:Lymphoid neoplasms in HIV-positive individuals in India. 1183 89

Primary cutaneous diffuse large B-cell lymphoma (DLBCL) is an uncommon lymphoma. Some authors have suggested that large B-cell lymphoma can be segregated based on anatomic site, with tumors of the lower extremity being unique. We report 15 cases of primary cutaneous DLBCL. Each case was analyzed immunohistochemically using antibodies specific for CD3, CD5, CD10, CD20, bcl-2, bcl-6, and p53. Polymerase chain reaction analysis for t(14;18)(q32;q21) also was performed. There were 13 men and 2 women (median age, 64 years). Thirteen tumors were composed predominantly of centroblasts, and 2 were immunoblastic. There was a median follow-up of 72 months. Of the 4 patients with primary cutaneous DLBCL of the lower extremity (thigh, knee, leg), 2 (50%) experienced a recurrence and 1 patient died of disease. In the non-lower extremity cases, 18% (2/11) recurred and no patients died of disease. We conclude that primary cutaneous DLBCL usually occurs in elderly patients with a male predominance. Recurrences are common, but death of disease is rare.
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PMID:Primary cutaneous diffuse large B-cell lymphoma: a clinicopathologic study of 15 cases. 1193 32

A Japanese male patient received various medications for his long-standing rheumatoid arthritis (stage IV, class II). He developed a mass on the right anterior chest wall after being treated with methotrexate (MTX) for 4 months. A biopsy of the mass showed it to be Epstein Barr virus (EBV)-associated lymphoma of B-cell phenotype stage IE (bulky mass), with positive EBV-encoded small RNAs (EBERs) in situ hybridization, EBV latent membrane protein-1 (LMP-1) negative, EB nuclear antigen-2 (ERNA-2) negative, CD20/L26 (+), CD45RO/UCHL-1 (-). A single band of the joined termini of the EBV genome was demonstrated in DNA extracted from the mass, suggesting a clonal disorder of the mass. Immunostaining of the mass with p53 antibody was also positive. With discontinuation of MTX and administration of chemotherapy, the tumor disappeared but recurred after 3 months. This case suggests that concordant p53 expression and latent EBV infection may play an important role in the pathogenesis of lymphomas arising in patients with rheumatoid arthritis who are immunosuppressed with MTX.
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PMID:Epstein-Barr virus-associated B-cell type non-Hodgkin's lymphoma with concurrent p53 protein expression in a rheumatoid arthritis patient treated with methotrexate. 1204 74

Histologically, the marginal zone pattern of the lymph node is characterized by lymphoid follicles with three distinct layers. The inner layer is composed of follicular center zones, the middle layer of darkly stained mantle zones, and the outer layer of marginal zones. However, the marginal zone pattern is rarely seen in reactive lymph nodes except for mesenteric lymph nodes. We describe the clinicopathologic, immunohistochemical and genotypic findings of six cases of reactive follicular hyperplasia exhibiting the marginal zone pattern. The patients comprised three males and three females (age range 24 to 63 years; medium 56 years). Follow-up data were obtained from five patients. None of them developed malignant lymphomas during the follow-up period of from 5 to 204 months (median 68 months). Histologically, the lesion was characterized by numerous lymphoid follicles and partial distortion of lymph node structure. Varying degrees of progressive transformation of the germinal center (PTGC) were noted in the four cases. The marginal zone pattern was observed in some or most of the lymphoid follicles including PTGC. The marginal zone B cells were small to medium-sized lymphocytes with round or slightly indented nuclei and a broad rim of pale cytoplasm. Some of them had a monocytoid appearance. They were CD20+, CD79a+, sIgM+/-, sIgD-, CD5-, CD10-, CD21-, CD23-, CD43-, CD45RO-, Bcl-6-, cyclin D1-, EMA- and p53-. A portion of them were Bcl-2 positive. Occasional large lymphoid cells with round or indented nuclei and moderate amounts of cytoplasm were observed in the marginal zone in four cases. These large lymphoid cells were usually CD20 positive, but Bcl-6 negative. A small number of them contained polytypic intracytoplasmic immunoglobulins. The polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. Recognition of unusual marginal zone hyperplasia in reactive lymph node lesions is important to avoid confusion with nodal involvement in various low-grade B cell lymphomas presenting a marginal zone distribution pattern.
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PMID:Follicular hyperplasia presenting with a marginal zone pattern in a reactive lymph node lesion. 1207 68

A retrospective study was performed to characterize malignant lymphomas of 16 Simian immunodeficiency virus (SIV)-infected rhesus monkeys (Macaca mulatta), 2-9 years of age, on the basis of clinical data, histologic and immunophenotypic results, and cell death indices compiled with the TdT-mediated X-duTP nick end labeling method. We particularly focused on providing immunohistochemical evidence of expression products of EBNA2, Bc12, c-Myc, P21, P53, and Bc16. Results were compared with data from the literature on human HIV-associated lymphomas. According to the updated Kiel classification, the lymphomas were classified as 11 centroblastic lymphomas, three immunoblastic lymphomas, one Burkitt-like lymphoma, and one immunocytoma. Using antibodies to CD20, the B-cell origin of tumor cells was demonstrated. SIV antigen was not demonstrated in the tumor cells. Infection with rhesus lymphocryptovirus was present in 94% of the monkeys. Lymphomas revealed expression of Bc12 in 15/16 (94%), c-Myc in 14/16 (88%), P21 in 10/ 16 (63%), P53 in 12/16 (75%), and Bc16 in 1/16 (6%) monkeys. This study provided evidence that the expression of these gene products, which are thought to play an important role in cell proliferation and apoptosis in HIV- and non-HIV-associated lymphomas, are also involved in the pathogenesis of lymphomas in SIV-infected rhesus monkeys. A tentative relationship between the described gene products and the cell death indices was established for the expression of Bc12. The present primate model represents a suitable animal model for studying the pathogenesis of AIDS-associated lymphomas.
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PMID:SIV-associated lymphomas in rhesus monkeys (Macaca mulatta) in comparison with HIV-associated lymphomas. 1210 18

Recent classifications of non-Hodgkin's lymphomas (NHL) have strictly individualized mantle cell lymphoma (MCL) on the basis of a combination of morphologic, immunophenotypic, and cytogenetic criteria. This clinicopathological entity now appears to be a biological and therapeutic model for the understanding and treatment of hematologic malignancies. The lymphomogenesis of MCL could be explained by a series of genetic abnormalities which occur at different steps of the disease: (1) mutation and/or loss of the ATM gene in centrocytic cells of the follicle mantle of lymph nodes, leading to the loss of ATM function, particularly involved during the V(D)J recombination process; (2) a t(11;14)(q13;q32) translocation which induces a constitutive Bcl-1/PRAD1/CCND1 expression, responsible for cell cycle activation of centrocytic cells characteristic of typical MCL; and (3) secondary additional chromosomal aberrations, such as a p53 mutation, observed in blastic transformation of MCL. Despite the evaluation of a number of treatment modalities, the optimal management of MCL has not yet been defined: (1) conventional and intensified chemotherapy and monoclonal anti-CD20 antibody therapy appear to be effective for the improvement of response rates and event-free or overall survivals; (2) combinations of different treatment modalities must be tested to modify the natural dismal outcome of the disease; and (3) innovative approaches should be developed. From this point of view, all these considerations offer a fine opportunity for extensive medical reflection.
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PMID:Mantle cell lymphoma: a biological and therapeutic paradigm. 1215 64


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